Following the description in this branch of the entity of winter Seasonal Affective Disorder, we have explored the use of light in the treatment of this condition. As light treatment is not universally effective for all patients with SAD, we have also explored pharmacological approaches to its treatment. Depue and others have suggested that brain dopaminergic pathways may be dysregulated in SAD. In previous studies, we have found that small subgroup of SAD patients can derive considerable benefit from dopaminergic agonists. In order to expand our earlier findings and further test the dopaminergic dysregulation theory of SAD, we undertook a placebo- controlled double-blind trial of a levodopa/carbidopa combination treatment for winter SAD. Over the past two years 50 drug-free medically healthy patients who met criteria for SAD and were depressed were given two-week placebo washout period. Those patients who remained significantly depressed were then randomized either to continued placebo therapy or to active medication for a further two weeks. Thirteen patients were randomized to continued placebo; eleven to the medication condition. Active medications consisted of approximately 5 mg/kg/day of levodopa for one week and 7 mg/kg/day for the second week, plus 100 mg/day of carbidopa throughout the two weeks. Blind raters assessed outcome by administering a structured interview. Data were analyzed by analysis of variance. For the group as a whole, there was no difference between responses to the two conditions. Nevertheless, among pre-menopausal females, responses to levodopa were dramatic and significantly better than those of placebo. This study raises the possibility that dopaminergic precursor therapy might be of specific value in pre-menopausal women, who make up the majority of the winter SAD population. Further research is necessary to determine whether pre-menopausal women make up a biologically distinct component of the winter SAD population.